A tough-to detect and alarmingly common intestinal disease may have a lot to do with India’s stunted children and their susceptibility to polio and rotavirus infections.
An infant receiving an oral polio vaccine. Credit: cdcglobal/Flickr, CC BY 2.0
In 2011, a team of scientists from the USA, the Netherlands and Bangladesh began a study to answer one mystery: More than 95% of children who contract paralytic polio in India have received more than 3 doses of the Oral Polio Vaccine. In Bangladesh, the oral rotavirus vaccine has shown to be effective only 43% of the time compared to 95% in Europe. What could be causing this vaccine inefficacy?
One hypothesis claims that oral polio vaccines and rotavirus vaccines are less likely to work in children suffering from a type of intestinal damage called environmental enteropathy (EE), thought to be common in developing nations. The group built a strategy to test this.
Characterised by inflamed small intestines, resulting in faulty nutrient absorption, EE is believed to result out of repeated exposure to harmful pathogens. In low-income countries, where sanitation is often inadequate, EE is thought to be pretty common, but being a subclinical disease, it does not always show symptoms and hence has proved difficult to study.
The only foolproof way to identify EE patients would be via a biopsy, but since invasive techniques are not an option for large-scale studies on young subjects, the investigators made do with what they felt was the next best thing. The scientists of the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries (PROVIDE) study diagnosed EE based on whether certain compounds were present in the subjects’ stool samples. These compounds, or biomarkers, have shown to be indicative of intestinal inflammation.
The scientists chose 700 infants in a Bangladeshi slum and tracked them from birth until one year of age. Their results, published in October 2015 in the journal EBioMedicine, showed that by the time the babies were 12 weeks old, over 80% of them were suffering from EE and 28.6% were malnourished.
Oral polio vaccine and oral rotavirus vaccine failed in 20.2% and 68.5% of the infants. In contrast, injected vaccines like those against tetanus and measles were almost always effective. These numbers indicated that EE could be predictive of oral vaccine failure as well as nutrition, and the team makes a case for interventions against malnutrition to be designed keeping this in mind.
Battered and bruised
The poliovirus and rotavirus are enteric pathogens: they enter orally or faecally and infects intestines. They spread chiefly through contact with contaminated water and faeces and so are directly associated with hygiene. EE patients’ intestinal linings have been battered by continuous infections and inflammations. “We suspect this prevents the replication of the live viruses that are part of the oral polio and rotavirus vaccines,” said William Petri from University of Virginia, one of the authors of the study. Injected vaccines, on the other hand, are unlikely to be affected by inflamed guts.
No longer able to absorb nutrients as well, the damaged gut of an EE patient does not respond to nutrient-based interventions, resulting in malnutrition.
There is enough reason to suspect that prevalence of EE is similarly high among Indians. The PROVIDE team is currently evaluating the results of a similar study they conducted in Kolkata in collaboration with the National Institute of Cholera and Enteric Disease (NICED, part of the Indian Council of Medical Research).
India’s Ministry of Health and Family Welfare had announced in November 2014 that they would soon be launching a policy to counter EE, but there has been no update since. Rakesh Kumar, Joint Secretary, who had made the announcement, did not reply to requests for the status of the proposed policy.
Meanwhile, two reports released in December 2015 revealed India’s mediocre performance as far as eradicating malnutrition is concerned. The Global Nutrition Report showed that 39% of India’s under-five population are stunted. The global average is 24%.
Better combat strategy needed
The PROVIDE study may be the most recent but it’s not the first to emphasise the dangers of enteric diseases. The ‘Interactions of Malnutrition & Enteric Infections: Consequences for Child Health and Development’ (MAL-ED) project investigated this across 8 countries – Peru, Brazil, Bangladesh, India, Pakistan, Tanzania, South Africa and Nepal.
Nevertheless, the PROVIDE study was more extensive, according to Petri. “The strength of PROVIDE was that vaccine responses were thoroughly measured and biomarkers of gut health, systemic inflammation and maternal health were comprehensively measured.”
The implications appear unanimous. Petri says that EE can be ameliorated by improvements in maternal health, improvements in sanitation to prevent the constant enteric infections, specific treatment or vaccination for certain infections that are more likely to cause EE, and nutritional supplementation for affected infants.
Gagandeep Kang from the Christian Medical College, Vellore, who was part of the MAL-ED project, also reiterated the importance of sanitation, hygiene and better feeding, but she expressed cautiousness as well, in an email. “The existence of a programme is insufficient. Implementation requires monitoring for quality. That rarely happens.”